protocol for the administration of intravenous vancomycin ......uncontrolled when printed review...

Signature:

Identifier:

NHSG/Guid/Vanc/ MGPG956

Review Date:

June 2020

Date Approved:

June 2018

Executive Sign-Off

This document has been endorsed by the Director of Pharmacy and Medicines Management

Uncontrolled when printed

Version 5

NHS Grampian

Acute Sector

NHS Grampian Staff Guidance for the Administration of Intravenous Vancomycin in Adults via Intermittent

(pulsed) Infusion

Co-ordinators:

Reviewer:

Approver:

Specialist Antibiotic Pharmacists

Chair; Antimicrobial Management Team

Medicine Guidelines and Policies Group

Signature: Signature: Signature:

UNCONTROLLED WHEN PRINTED Review Date: June 2020 NHSG/Guid/Vanc/MPGP956 - i - Guidance for the Administration of Intravenous Vancomycin in Adults via Intermittent (pulsed) Infusion - Version 5

Title: NHS Grampian Staff Guidance for the Administration of Intravenous Vancomycin in Adults via Intermittent (pulsed) Infusion

Unique Identifier: NHSG/Guid/Vanc/MGPG956 Replaces: NHSG/Guid/Vanc/MGPG636, Version 4

Across NHS Boards

Organisation Wide

Directorate Clinical Service Sub Department Area

Acute Sector

This controlled document shall not be copied in part or whole without the express permission of the author or the author’s representative. Lead Author/Co-ordinator: Specialist Antibiotic Pharmacists Subject (as per document registration categories):

Prescribing Policy

Key word(s): Vancomycin, therapeutic, monitoring, intravenous,

administration, antibiotics, antimicrobials, dosing guideline, TDM, therapeutic drug monitoring, glycopeptide antibacterials, pulsed, intermittent

Process Document: Policy, Protocol, Procedure or Guideline

Guideline

Document application: NHS Grampian

Purpose/description: To provide guidance for medical, nursing and pharmacy

staff about how to dose, monitor and administer intravenous vancomycin safely and effectively in adults.

Responsibilities for implementation: Organisational: Chief Executive and Management Teams Corporate: Senior Managers Departmental: Heads of Service/Clinical Leads Area: Line Managers Hospital/Interface services: Assistant General Managers and Group Clinical Directors Operational Management Unit:

Unit Operational Managers

Policy statement: It is the responsibility of all staff to ensure that they are working to the most up to date and relevant policies, protocols procedures.

Review:

This policy will be reviewed in two years or sooner if current treatment recommendations change

UNCONTROLLED WHEN PRINTED Review Date: June 2020 NHSG/Guid/Vanc/MPGP956 - ii - Guidance for the Administration of Intravenous Vancomycin in Adults via Intermittent (pulsed) Infusion - Version 5

This document is also available in large print and other formats and languages, upon request.

Please call NHS Grampian Corporate Communications on (01224) 551116 or (01224)

552245. Responsibilities for review of this document: Specialist Antibiotic Pharmacists

Responsibilities for ensuring registration of this document on the NHS Grampian Information/Document Silo:

Development Pharmacist – Medicines Management

Physical location of the original of this document:

Pharmacy and Medicines Directorate

Job/group title of those who have control over this document:

Antimicrobial Management Team

Responsibilities for disseminating document as per distribution list:

Specialist Antibiotic Pharmacists

Revision History:

Revision Date

Previous Revision Date

Summary of Changes (Descriptive summary of the changes made)

Changes Marked* (Identify page numbers and section heading )

Feb 2017 Mar 2014 Review of exclusions/cautions Rate of infusion – units amended in line with PAR Added reference to the antimicrobial calculator and app and printing off the results. New note added regarding loading dose. Note re usual maximum dose added Added new prescription chart. Added new screenshot of calculator Added maintain body weight table Added info sheet for nurses and prescribers.

p2 p3 p4 p5 p8 Appendix 1 Appendix 2 Appendix 3 Appendix 4

* Changes marked should detail the section(s) of the document that have been amended, i.e. page number and section heading.

UNCONTROLLED WHEN PRINTED Review Date: June 2020 NHSG/Guid/Vanc/MPGP956 - 1 - Guidance for the Administration of Intravenous Vancomycin in Adults via Intermittent (pulsed) Infusion - Version 5

NHS Grampian Staff Guidance for the Administration of Intravenous Vancomycin in Adults via Intermittent (pulsed) Infusion Contents Page No

Introduction and Rationale ................................................................................................... 2

Exclusions: ........................................................................................................................... 2

Cautions: .............................................................................................................................. 2

Vancomycin Administration .................................................................................................. 3

STEP 1: Calculate and prescribe the loading dose and maintenance dose of vancomycin . 5

STEP 2: Monitor the vancomycin concentration and reassess the dose ............................. 7

Table 3: Adjustment of Vancomycin dosage regimen .......................................................... 8

References .......................................................................................................................... 9

Consultation List .................................................................................................................. 9

Appendix 1: Adult Intravenous Vancomycin Intermittent Infusion (Pulsed): Prescription, Administration & Monitoring Record .................................................................................. 10

Appendix 2: Example of Vancomycin Calculator Screenshot ............................................ 12

Appendix 3: Maximum Body Weight table – for creatinine clearance calculations ............. 13

Appendix 4: NHS Grampian Adult INTRAVENOUS VANCOMYCIN Intermittent Infusion (pulsed) Information Sheet for NURSES & PRESCRIBERS .............................................. 14 Glossary of abbreviations ABW Actual body weight CrCl Creatinine Clearance eGFR estimated Glomerular Filtration Rate IBW Ideal body weight MBW Maximum Body Weight MIC Minimum Inhibitory Concentration MRSA Meticillin-resistant Staphylococcus aureus NSAIDs Non-steroidal anti-inflammatory drugs


Acute Sector

NHS Grampian Staff Guidance for the Administration of Intravenous Vancomycin in Adults via Intermittent

(pulsed) Infusion Introduction and Rationale This protocol details the dosing, prescribing, monitoring and administration of intravenous vancomycin as an intermittent (pulsed) infusion 1. Vancomycin can also be administered as a continuous infusion, when practical, for patients with severe or deep-seated infections (e.g. pneumonia, endocarditis, bone and joint infections). In NHS Grampian only Intensive Care use continuous infusion which is not covered in this guidance– refer to ICU protocol. Vancomycin is a glycopeptide antibacterial used in the treatment of serious staphylococcal or other gram-positive infections when other drugs such as the penicillins cannot be used because of resistance or patient intolerance. It is used particularly in the treatment of meticillin-resistant staphylococcal infections (MRSA)2. Refer to NHSG Infection Management Guidelines: Empirical Antibiotic Therapy for indications. Vancomycin works most effectively when the levels of the drug remain above the minimum inhibitory concentration (MIC) for the target organism at all times. Trough levels of vancomycin therefore require to be monitored throughout treatment and these should be 10-15mg/L in standard infections4. On the basis of the potential to improve penetration, to increase the probability of optimal target serum concentrations, and to improve the clinical outcomes of complicated infections, such as bacteraemia, endocarditis, osteomyelitis, meningitis and hospital-acquired pneumonia caused by Staphlococcus aureus (S.aureus), trough serum vancomycin concentrations of 15-20mg/L are recommended4,5. This range is also recommended for less sensitive strains of S. aureus4. Exclusions: • Children <16 years of age. • Patients who are allergic/hypersensitive to vancomycin • Treatment of Clostridium difficile Infection (vancomycin should be given orally) • Patients in intensive care who require a continuous vancomycin infusion Cautions: Advice should be sought from Microbiology or an Infection Specialist on treatment options if any of the following apply: • Patients with previous hearing loss • Patients treated in renal units or receiving haemodialysis or haemofiltration (contact

the Renal unit for advice and follow the local unit protocol) • Treatment of ventriculitis or ventriculoperitoneal shunt infections (contact neurology

specialist for advice).

https://foi.nhsgrampian.org/globalassets/foidocument/foi-public-documents1---all-documents/NHSGEmpA.pdf

https://foi.nhsgrampian.org/globalassets/foidocument/foi-public-documents1---all-documents/NHSGEmpA.pdf


• Use with caution in patients with sensitivity to other glycopeptides (eg teicoplanin, dalbavancin) due to possibility of cross-sensitivity.

• Where possible, avoid co-administration with: o Gentamicin (aminoglycosides) o Nonsteroidal anti-inflammatory drugs (NSAIDs) o Amphotericin o Potent diuretics o Angiotensin converting enzyme inhibitors (ACE inhibitors).

This list is not exhaustive – consult the Summary of Product Characteristics (SmPC) for a full list (www.medicines.org.uk). Vancomycin Administration Vancomycin is very irritating to tissue, and should not be given intramuscularly as this causes injection site necrosis. It must be given by slow intravenous infusion using a dilute solution to reduce the risk of tissue necrosis if extravasation occurs. Vancomycin should not be given rapidly due to the risk of infusion reactions. The intravenous use of vancomycin may be associated with the so-called 'red-neck' or 'red-man' syndrome, characterised by erythema, flushing, or rash over the face and upper torso, and sometimes by hypotension and shock-like symptoms. The effect appears to be due in part to the release of histamine and is usually related to rapid infusion1. It may also cause pain or muscle spasm. In order to avoid these risks: • Vancomycin must ALWAYS be administered by intravenous INFUSION in either

0.9% Sodium Chloride or 5% Glucose • Final concentration: NOT MORE THAN 5mg/mL for peripheral administration • Rate of infusion: NO FASTER THAN 500mg/hour6.

http://www.medicines.org.uk/


Prescribing and documentation Vancomycin should be prescribed on the Adult Intravenous Vancomycin Intermittent Infusion (Pulsed) Prescription, Administration & Monitoring Record (PAMR) (Appendix 1), and reference to this should be made on the patient’s main prescription chart as shown below;

An online calculator and/or Antimicrobial Companion app is available and should be used to calculate the initial dose requirements. It is recommended practice to print off the calculator result (Appendix 2 sample), add the patient’s name and CHI and file with the prescription chart (this allows a double check to ensure the dosing is correct).


STEP 1: Calculate and prescribe the loading dose and maintenance dose of vancomycin • To reduce the risk of mortality, commence vancomycin administration within 1 hour

of recognising sepsis • If creatinine is known – use the online calculator (preferred method). The guidance

in Table 1 (Initial LOADING dose) and Table 2 (MAINTENANCE dose) can be used if the online calculator is not available. The dose amount and dosage interval are based on estimated creatinine clearance (Box 1) and actual body weight.

• If creatinine is not known – calculate and prescribe a loading dose based on actual

body weight (Table 1). Calculate the maintenance dose once the creatinine is available.

Box 1: Estimation of creatinine clearance (CrCl)

The following ‘Cockcroft Gault’ equation can be used to estimate creatinine clearance (CrCl): CrCl [140-age (years)] x weight* (kg) x 1.23 (male) or 1.04 (female) (mL/min) = serum creatinine∆ (micromol / L) Cautions: • *Use actual body weight or maximum body weight for patient’s height, whichever is

lower. For maximum body weight see Appendix 3 - Body Weight Table. • ∆In patients with low creatinine (<60micromol/L), use 60 micromol/L to avoid

overestimating creatinine clearance due to low muscle mass. • Note: Use of estimated glomerular filtration rate (eGFR) from labs is not recommended

for calculation of vancomycin doses.

http://nhsgintranet.grampian.scot.nhs.uk/systemsresources/Systems%20%20Resources%20Documents/NHSGVanCal20120214.xls


Loading Infusion N.B. The loading dose is based on weight only, so does not take renal function into account. When using the online calculator, on rare occasions a patient’s clearance of vancomycin may be so high that the maintenance dose is higher than the loading dose. In these circumstances, the loading dose given should be the higher of the calculated loading and maintenance doses i.e. if loading dose is calculated as lower than maintenance dose then give the calculated maintenance dose as a loading dose instead. Table 1: Initial Vancomycin LOADING Dose

Actual Body Weight (ABW)

Dose Volume (0.9% Sodium Chloride†)

Duration of infusion

<40kg 750mg 250mL 1.5 hours 40-59kg 1000mg 250mL 2 hours 60-90kg 1500mg 500mL 3 hours >90kg 2000mg 500mL 4 hours

†Glucose 5% can be used in patients with sodium restriction. Maintenance Dosage Regimen • Give the first maintenance infusion 12, 24 or 48 hours after the loading infusion

according to dose interval provided by the online calculator or Table 2 (below). Table 2: Vancomycin MAINTENANCE dosage regimen

VANCOMYCIN PULSED INFUSION – INITIAL MAINTENANCE DOSAGE GUIDELINES

CrCl (mL/min) Dose Dosing Interval

Volume of sodium chloride 0.9%‡

< 20 500mg over 1 hour 48 hours 250mL 20-29 500mg over 1 hour 24 hours 250mL 30-39 750mg over 1.5 hours 24 hours 250mL 40-54 500mg over 1 hour 12 hours 250mL 55-74 750mg over 1.5 hours 12 hours 250mL 75-89 1000mg over 2 hours 12 hours 250mL

90-110 1250mg over 2.5 hours 12 hours 250mL >110 1500mg over 3 hours 12 hours 500mL

‡ Glucose 5% may be used in patients with sodium restriction. • Doses up to 2000mg can be diluted in 500mL fluid. • The daily dose can be split into 3 equal doses and given 8 hourly. This approach is

especially useful for patients who require high doses as it produces higher trough concentrations, and reduces the time of each individual infusion. For example, 1500mg 12 hourly (3000mg per day) could be prescribed as 1000mg 8 hourly, and 750mg 12 hourly (1500mg per day) as 500mg 8 hourly. For further advice discuss with pharmacist or microbiology.


STEP 2: Monitor the vancomycin concentration and reassess the dose

Concentrations are meaningless unless the dose and sample times are recorded accurately. • Due to wide variability in the handling of vancomycin, early analysis of a vancomycin

concentration is required to ensure that the dosage regimen is appropriate. • Take a trough sample (pre-dose) within 24-48 hours of starting therapy then every 2-

3 days, or daily if the patient has unstable renal function. • Monitor creatinine daily. • Record the exact time of all vancomycin samples on the Adult Intravenous

Vancomycin Intermittent Infusion (pulsed) PAMR AND on the sample request form along with the last time of administration.

• If the renal function is stable, give the next dose before the trough result is available. If renal function is deteriorating, withhold until the result is available then follow the advice in Table 3.

Target trough vancomycin concentrations • Target trough concentration range: 10 – 20mg/L • If the patient is seriously ill (severe or deep-seated infection), the target trough

concentration range is 15 - 20mg/L. If the measured concentration is <15mg/L, consider increasing the dose amount or reducing the dosage interval (see comment on 8 hourly dosing under table 2 above).

• If the patient is failing to respond, seek advice from microbiology or an infection specialist.

Adjustment of the vancomycin dosage regimen • Always check that the dosage history and sampling time are appropriate before

interpreting the result. • Seek advice from pharmacy or microbiology if you need help to interpret the result. If the measured concentration is unexpectedly HIGH or LOW If the measured concentration is unexpectedly HIGH or LOW, consider the following: • Were the dose and sample times recorded accurately? • Was the correct dose administered? • Was the sample taken from the line used to administer the drug? • Was the sample taken during drug administration? • Has renal function declined or improved? • Does the patient have oedema or ascites?


Table 3: Adjustment of Vancomycin dosage regimen Vancomycin Concentration Suggested Dose Change

<10mg/L Increase dose by 50% and consider reducing the dosage interval or seek advice*

10-15mg/L If the patient is responding, maintain the present dosage regimen If the patient is seriously ill, consider increasing the dose amount or reducing the dosage interval to achieve a trough level of 15-20mg/L

15 - 20mg/L Maintain the present dosage regimen >20mg/L Stop until <20mg/L and seek advice

*Usual maximum daily dose is 3g; discuss with senior medical staff/pharmacy before increasing above this. If in doubt, take another sample before modifying the dosage regimen and / or contact pharmacy for advice. General points • Record the exact times of all measured concentrations on the Adult Intravenous

Vancomycin Intermittent Infusion (pulsed) PAMR. • Reassess the dose and continue or prescribe a dosage change. • Assess daily for ongoing need for vancomycin and for signs of toxicity • Document the action taken in the medical notes and on the Adult Intravenous

Vancomycin Intermittent Infusion (pulsed) PAMR. • Review the need for vancomycin daily. Box 2: Toxicity • Monitor creatinine daily. Seek advice if renal function is unstable (e.g. a change in

creatinine of >15-20%) • Signs of renal toxicity include increase in creatinine or decrease in urine output /

oliguria. • Consider an alternative agent if creatinine is rising or the patient becomes oliguric. • Vancomycin may increase the risk of aminoglycoside induced ototoxicity – use

caution if co-prescribing. STEP 3: Assess daily the ongoing need for vancomycin and for signs of toxicity • Review the need for vancomycin daily. • Consider adjusting the dose regimen or using an alternative agent if renal function

changes. See Box 2 above for signs of renal toxicity Consider changing to an oral alternative – refer to the IV to Oral Switch (IVOST policy.

https://foi.nhsgrampian.org/globalassets/foidocument/foi-public-documents1---all-documents/NHSGIVOST.pdf


Information Sheet: See information sheet (Appendix 4) for nurses and prescribers, highlighting key safety checks to ensure that all appropriate prescribing details and monitoring have been documented before a dose is administered. For further advice contact: Antibiotic Pharmacists Bleep 3933, Ext: 51048. Ward Clinical Pharmacists - see ward information for contact details. Medical Microbiology via switchboard. References 1. Scottish Antimicrobial Prescribing Group. Intravenous Vancomycin Use in Adults

Intermittent (Pulsed) Infusion. January 2017. https://www.sapg.scot/media/2936/sapg_intravenous_vancomycin_adults__pulsed_infusion_.pdf

2. Martindale: The Complete Drug Reference. Accessed online via www.micromedex solutions.com.

3. Thomson et al. Development and evaluation of vancomycin dosage guidelines designed to achieve new target concentrations. Journal of Antimicrobial Chemotherapy, 2009; 63: 1050-1057.

4. British National Formulary 72. Sept 2016- Mar 2017. Accessed via www.bnf.org. 5. Rybak et al. Vancomycin Therapeutic Guidelines: A Summary of Consensus

Recommendations from the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society for Infectious Diseases Pharmacists. Clinical Infectious Diseases 2009; 49: 325-7.

6. Summary of Product Characteristics for Vancomycin 1g Powder for Solution for Infusion (Wockhardt UK Ltd). Accessed via www.medicines.org.uk.

Consultation List Antimicrobial Management Team Members; Dr Ian Gould, Medical Microbiology Dr Sandy Mackenzie, Consultant, Infectious Diseases Dr Ivan Tonna, Consultant, Infectious Diseases Pamela Harrison, Infection Control Manager Gillian Macartney, Antibiotic Pharmacist Comments received from: Antimicrobial Management Team Medicines Guidelines and Policies Group Records Standards Group

https://www.sapg.scot/media/2936/sapg_intravenous_vancomycin_adults__pulsed_infusion_.pdf

https://www.sapg.scot/media/2936/sapg_intravenous_vancomycin_adults__pulsed_infusion_.pdf

http://www.medicinescomplete.com/

http://www.medicinescomplete.com/

http://www.bnf.org/

http://www.medicines.org.uk/


Appendix 1: Adult Intravenous Vancomycin Intermittent Infusion (Pulsed): Prescription, Administration & Monitoring Record


Appendix 1: Adult Intravenous Vancomycin Intermittent Infusion (Pulsed): Prescription, Administration & Monitoring Record (Continued)

UNCONTROLLED WHEN PRINTED Review Date: June 2020 NHSG/Guid/Vanc/MPGP956 - 12 – Guidance for the Administration of Intravenous Vancomycin in Adults via Intermittent (pulsed) Infusion - Version 5

Appendix 2: Example of Vancomycin Calculator Screenshot


Appendix 3: Maximum Body Weight table – for creatinine clearance calculations This table can be used to determine whether patients are classed as ‘obese’ (>20% over Ideal Body Weight) and to determine the Maximum Body Weight for use in the Cockcroft Gault equation (see Box 1).

Maximum Body Weight (MBW) table (= Ideal Body Weight + 20%) Height (ft inches) Height (cm) MBW (kg) MALE MBW (kg) FEMALE

4’ 8” 142 49 43

4’ 9” 145 52 47

4’ 10” 147 54 49

4’ 11” 150 58 52

5’ 0” 152 60 55

5’ 1” 155 62 58

5’ 2” 158 66 60

5’ 3” 160 68 62

5’ 4” 163 71 66

5’ 5” 165 74 68

5’ 6” 168 77 71

5’ 7” 170 79 74

5’ 8” 173 82 77

5’ 9” 175 85 79

5’ 10” 178 88 82

5’ 11” 180 90 85 6’ 0” 183 94 88

6’ 1” 185 96 90

6’ 2” 188 98 94

6’ 3” 191 101 97

6’ 4” 193 104 99

6’ 5” 195 107 101

6’6” 198 109 105

6’ 7” 201 113 108

6’ 8” 203 115 110


Appendix 4: NHS Grampian Adult INTRAVENOUS VANCOMYCIN Intermittent Infusion (pulsed) Information Sheet for NURSES & PRESCRIBERS

This information sheet highlights the key safety checks to ensure that all appropriate prescribing details and monitoring have been documented before a vancomycin dose is safely administered. Before administering the first (loading) dose: 1. Check prescriber has used the Vancomycin prescription chart – see example below:

2. Check if prescriber has printed off results from online

calculator, added patient details, and filed with prescription charts (this gives a double check that dose is correct) – see example: 3. If online calculator not used/ printed off, see loading dose table on prescription chart to check this corresponds to patient’s weight. 4. Ensure the time of administration is accurately noted using

24 hour clock.

Before administering maintenance doses: 1. If there are any issues with the patient’s IV access, inform medical staff well in advance of the

next dose being required, as any delays will significantly affect the efficacy of antibiotic treatment.

2. If infusion not started within about 10-15 minutes of the prescribed time then accurately record the time (24 hour clock) as this will impact on interpretation of levels.

3. A trough level (immediately before dose given) should be taken within 48 hours of starting therapy and then the dose should be administered as prescribed i.e. do not wait for the result.

4. If a trough level has been recorded on the prescription chart, check that the prescriber has completed the Y/N box to indicate whether any dosage change is required.

5. If in doubt, check with prescriber / medical staff/ pharmacist before administering.

→ reference to this chart should be made on the patient’s main prescription chart as shown below and opposite: